KEYTRUDA Now First Anti-PD-1 Therapy Approved for Patients with
Advanced Cervical Cancer and Disease Progression on or After Chemotherapy

June 12, 2018 04:06 PM Eastern Daylight Time

KENILWORTH, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada,
today announced that the U.S. Food and Drug Administration (FDA) has
approved KEYTRUDA®, the company’s anti-PD-1 therapy, for the
treatment of patients with recurrent or metastatic cervical cancer with
disease progression on or after chemotherapy whose tumors express PD-L1
[Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test.This indication is approved under the FDA’s accelerated approval
regulations based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials.

“KEYTRUDA is now the first anti-PD-1 therapy approved for the treatment
of advanced cervical cancer, providing an important new second-line
option for certain patients with this disease,” said Dr. Roy Baynes,
senior vice president and head of global clinical development, chief
medical officer, Merck Research Laboratories. “This approval also marks
the first indication for KEYTRUDA in a gynecologic cancer and reflects
our ongoing commitment to bring forward innovative treatment options
across a broad range of cancers, including cancers that
disproportionately affect women.”

Immune-mediated adverse reactions occurred with KEYTRUDA, including
pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe
skin reactions, and solid organ transplant rejection. Based on the
severity of the adverse reaction, KEYTRUDA should be withheld or
discontinued and corticosteroids administered if appropriate. KEYTRUDA
can also cause severe or life-threatening infusion-related reactions.
Monitor patients for signs and symptoms of infusion-related reactions;
for Grade 3 or 4 reactions, stop infusion and permanently discontinue
KEYTRUDA. Based on its mechanism of action, KEYTRUDA can cause fetal
harm when administered to a pregnant woman. Female patients of
reproductive potential should be advised of the potential hazard to a
fetus. For more information, see “Selected Important Safety Information”
below.

"Even with the many advances observed across gynecologic cancers, new
treatment options have been lacking for previously treated patients with
advanced cervical cancer,” said Dr. Bradley Monk, oncologist with
Arizona Oncology, medical director of US Oncology Research Gynecology
Program and professor of obstetrics and gynecology at University of
Arizona’s College of Medicine and Creighton University School of
Medicine. “The approval of KEYTRUDA in this indication is important news
– and as an oncologist, it is exciting to see a much needed option made
available to these patients.”

“This approval is welcome news for patients, who now have another option
in their fight against this serious disease,” said Tamika Felder,
founder and chief visionary officer, Cervivor.

Data Supporting the Approval

The efficacy of KEYTRUDA was investigated in 98 patients with recurrent
or metastatic cervical cancer enrolled in a single cohort (Cohort E) in
study KEYNOTE-158, a multi-center, non-randomized, open-label,
multi-cohort trial. The trial excluded patients with autoimmune disease
or a medical condition that required immunosuppression. Patients were
treated with KEYTRUDA intravenously at a dose of 200 mg every three
weeks until unacceptable toxicity or documented disease progression.
Patients with initial radiographic disease progression could receive
additional doses of treatment during confirmation of progression unless
disease progression was symptomatic, was rapidly progressive, required
urgent intervention, or occurred with a decline in performance status.
Patients without disease progression could be treated for up to 24
months. Assessment of tumor status was performed every nine weeks for
the first 12 months, and every 12 weeks thereafter. The major efficacy
outcome measures were objective response rate (ORR) according to
Response Evaluation Criteria In Solid Tumors (RECIST) 1.1, as assessed
by blinded independent central review, and duration of response (DOR).

Among the 98 patients in Cohort E, 77 (79%) had tumors that expressed
PD-L1 with a CPS ≥1 and received at least one line of chemotherapy in
the metastatic setting. PD-L1 status was determined using the PD-L1 IHC
22C3 pharmDx Kit. The baseline characteristics of these 77 patients
were: median age was 45 years (range, 27 to 75 years); 81 percent were
White, 14 percent Asian, and three percent Black; ECOG PS was 0 (32%) or
1 (68%); 92 percent had squamous cell carcinoma, six percent
adenocarcinoma, and one percent adenosquamous histology; 95 percent had
M1 disease and five percent had recurrent disease; 35 percent had one
and 65 percent had two or more prior lines of therapy in the recurrent
or metastatic setting.

For the 77 patients whose tumors expressed PD-L1 with a CPS ≥1, the ORR
was 14.3 percent (95% CI, 7.4-24.1), with a complete response rate of
2.6 percent and partial response rate of 11.7 percent. Among the 11
responding patients, median DOR was not yet reached (range, 4.1 to 18.6+
months) and 91 percent experienced a duration of response of six months
or longer. The median follow-up time was 11.7 months (range, 0.6 to 22.7
months). No responses were observed in patients whose tumors did not
have PD-L1 expression (CPS<1).

KEYTRUDA is an anti-PD-1 therapy that works by increasing the ability of
the body's immune system to help detect and fight tumor cells. KEYTRUDA
is a humanized monoclonal antibody that blocks the interaction between
PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes
which may affect both tumor cells and healthy cells.

Merck has the industry's largest immuno-oncology clinical research
program, which currently involves more than 750 trials studying KEYTRUDA
across a wide variety of cancers and treatment settings. The KEYTRUDA
clinical program seeks to understand the role of KEYTRUDA across cancers
and the factors that may predict a patient's likelihood of benefiting
from treatment with KEYTRUDA, including exploring several different
biomarkers.

KEYTRUDA® (pembrolizumab) Indications and
Dosing

Melanoma

KEYTRUDA is indicated for the treatment of patients with unresectable or
metastatic melanoma at a fixed dose of 200 mg every three weeks until
disease progression or unacceptable toxicity.

Lung Cancer

KEYTRUDA, as a single agent, is indicated for the first-line treatment
of patients with metastatic non-small cell lung cancer (NSCLC) whose
tumors have high PD-L1 expression [tumor proportion score (TPS) ≥50%] as
determined by an FDA-approved test, with no EGFR or ALK genomic tumor
aberrations.

KEYTRUDA, as a single agent, is also indicated for the treatment of
patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥1%) as
determined by an FDA-approved test, with disease progression on or after
platinum-containing chemotherapy. Patients with EGFR or ALK genomic
tumor aberrations should have disease progression on FDA-approved
therapy for these aberrations prior to receiving KEYTRUDA.

KEYTRUDA, in combination with pemetrexed and carboplatin, is indicated
for the first-line treatment of patients with metastatic nonsquamous
NSCLC. This indication is approved under accelerated approval based on
tumor response rate and progression-free survival. Continued approval
for this indication may be contingent upon verification and description
of clinical benefit in the confirmatory trials.

In metastatic NSCLC, KEYTRUDA is administered at a fixed dose of 200 mg
every three weeks until disease progression, unacceptable toxicity, or
up to 24 months in patients without disease progression.

When administering KEYTRUDA in combination with chemotherapy, KEYTRUDA
should be administered prior to chemotherapy when given on the same day.
See also the Prescribing Information for pemetrexed and carboplatin.

Head and Neck Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or
metastatic head and neck squamous cell carcinoma (HNSCC) with disease
progression on or after platinum-containing chemotherapy. This
indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. In HNSCC, KEYTRUDA is
administered at a fixed dose of 200 mg every three weeks until disease
progression, unacceptable toxicity, or up to 24 months in patients
without disease progression.

Classical Hodgkin Lymphoma

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with refractory classical Hodgkin lymphoma (cHL), or who have relapsed
after three or more prior lines of therapy. This indication is approved
under accelerated approval based on tumor response rate and durability
of response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. In adults with cHL, KEYTRUDA is administered at a
fixed dose of 200 mg every three weeks until disease progression or
unacceptable toxicity, or up to 24 months in patients without disease
progression. In pediatric patients with cHL, KEYTRUDA is administered at
a dose of 2 mg/kg (up to a maximum of 200 mg) every three weeks until
disease progression or unacceptable toxicity, or up to 24 months in
patients without disease progression.

Urothelial Carcinoma

KEYTRUDA is indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who are not eligible for
cisplatin-containing chemotherapy. This indication is approved under
accelerated approval based on tumor response rate and duration of
response. Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials.

KEYTRUDA is also indicated for the treatment of patients with locally
advanced or metastatic urothelial carcinoma who have disease progression
during or following platinum-containing chemotherapy or within 12 months
of neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy.

In locally advanced or metastatic urothelial carcinoma, KEYTRUDA is
administered at a fixed dose of 200 mg every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression.

Microsatellite Instability-High (MSI-H) Cancer

KEYTRUDA is indicated for the treatment of adult and pediatric patients
with unresectable or metastatic microsatellite instability-high (MSI-H)
or mismatch repair deficient (dMMR)

solid tumors that have progressed following prior treatment and who
have no satisfactory alternative treatment options, or

colorectal cancer that has progressed following treatment with
fluoropyrimidine, oxaliplatin, and irinotecan.

This indication is approved under accelerated approval based on tumor
response rate and durability of response. Continued approval for this
indication may be contingent upon verification and description of
clinical benefit in the confirmatory trials. The safety and
effectiveness of KEYTRUDA in pediatric patients with MSI-H central
nervous system cancers have not been established.

In adult patients with MSI-H cancer, KEYTRUDA is administered at a fixed
dose of 200 mg every three weeks until disease progression, unacceptable
toxicity, or up to 24 months in patients without disease progression. In
children with MSI-H cancer, KEYTRUDA is administered at a dose of 2
mg/kg (up to a maximum of 200 mg) every three weeks until disease
progression or unacceptable toxicity, or up to 24 months in patients
without disease progression.

Gastric Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent
locally advanced or metastatic gastric or gastroesophageal junction
(GEJ) adenocarcinoma whose tumors express PD-L1 [Combined Positive Score
(CPS) ≥1] as determined by an FDA-approved test, with disease
progression on or after two or more prior lines of therapy including
fluoropyrimidine- and platinum-containing chemotherapy and if
appropriate, HER2/neu-targeted therapy. This indication is approved
under accelerated approval based on tumor response rate and durability
of response. Continued approval for this indication may be contingent
upon verification and description of clinical benefit in the
confirmatory trials. The recommended dose of KEYTRUDA is 200 mg every
three weeks until disease progression, unacceptable toxicity, or up to
24 months in patients without disease progression.

Cervical Cancer

KEYTRUDA is indicated for the treatment of patients with recurrent or
metastatic cervical cancer with disease progression on or after
chemotherapy whose tumors express PD-L1 (CPS ≥1) as determined by an
FDA-approved test. This indication is approved under accelerated
approval based on tumor response rate and durability of response.
Continued approval for this indication may be contingent upon
verification and description of clinical benefit in the confirmatory
trials. The recommended dose of KEYTRUDA is 200 mg every three weeks
until disease progression, unacceptable toxicity or up to 24 months in
patients without disease progression.

KEYTRUDA can cause thyroid disorders, including hyperthyroidism,
hypothyroidism, and thyroiditis. Hyperthyroidism occurred in 96 (3.4%)
of 2799 patients receiving KEYTRUDA, including Grade 2 (0.8%) and 3
(0.1%) hyperthyroidism. Hypothyroidism occurred in 237 (8.5%) of 2799
patients receiving KEYTRUDA, including Grade 2 (6.2%) and 3 (0.1%)
hypothyroidism. Thyroiditis occurred in 16 (0.6%) of 2799 patients
receiving KEYTRUDA, including Grade 2 (0.3%) thyroiditis. Monitor
patients for changes in thyroid function (at the start of treatment,
periodically during treatment, and as indicated based on clinical
evaluation) and for clinical signs and symptoms of thyroid disorders.
Administer replacement hormones for hypothyroidism and manage
hyperthyroidism with thionamides and beta-blockers as appropriate.
Withhold or discontinue KEYTRUDA for Grade 3 or 4 hyperthyroidism.

KEYTRUDA can cause type 1 diabetes mellitus, including diabetic
ketoacidosis, which have been reported in 6 (0.2%) of 2799 patients.
Monitor patients for hyperglycemia or other signs and symptoms of
diabetes. Administer insulin for type 1 diabetes, and withhold KEYTRUDA
and administer antihyperglycemics in patients with severe hyperglycemia.

Immune-mediated rashes, including Stevens-Johnson syndrome (SJS), toxic
epidermal necrolysis (TEN) (some cases with fatal outcome), exfoliative
dermatitis, and bullous pemphigoid, can occur. Monitor patients for
suspected severe skin reactions and based on the severity of the adverse
reaction, withhold or permanently discontinue KEYTRUDA and administer
corticosteroids. For signs or symptoms of SJS or TEN, withhold KEYTRUDA
and refer the patient for specialized care for assessment and treatment.
If SJS or TEN is confirmed, permanently discontinue KEYTRUDA.

Immune-mediated adverse reactions, which may be severe or fatal, can
occur in any organ system or tissue in patients receiving KEYTRUDA.
While immune-mediated adverse reactions usually occur during treatment
with PD-1/PD-L1 blocking antibodies, they may occur after
discontinuation of treatment. For suspected immune-mediated adverse
reactions, ensure adequate evaluation to confirm etiology or exclude
other causes. Based on the severity of the adverse reaction, withhold
KEYTRUDA and administer corticosteroids. Upon improvement to Grade 1 or
less, initiate corticosteroid taper and continue to taper over at least
1 month. Based on limited data from clinical studies in patients whose
immune-related adverse reactions could not be controlled with
corticosteroid use, administration of other systemic immunosuppressants
can be considered. Resume KEYTRUDA when the adverse reaction remains at
Grade 1 or less following corticosteroid taper. Permanently discontinue
KEYTRUDA for any Grade 3 immune-mediated adverse reaction that recurs
and for any life-threatening immune-mediated adverse reaction.

The following clinically significant immune-mediated adverse reactions
occurred in less than 1% (unless otherwise indicated) of 2799 patients:
arthritis (1.5%), uveitis, myositis, Guillain-Barré syndrome, myasthenia
gravis, vasculitis, pancreatitis, hemolytic anemia, and partial seizures
arising in a patient with inflammatory foci in brain parenchyma. In
addition, myelitis and myocarditis were reported in other clinical
trials, including cHL, and postmarketing use.

Solid organ transplant rejection has been reported in postmarketing use
of KEYTRUDA. Treatment with KEYTRUDA may increase the risk of rejection
in solid organ transplant recipients. Consider the benefit of treatment
with KEYTRUDA vs the risk of possible organ rejection in these patients.

KEYTRUDA can cause severe or life-threatening infusion-related
reactions, including hypersensitivity and anaphylaxis, which have been
reported in 6 (0.2%) of 2799 patients. Monitor patients for signs and
symptoms of infusion-related reactions, including rigors, chills,
wheezing, pruritus, flushing, rash, hypotension, hypoxemia, and fever.
For Grade 3 or 4 reactions, stop infusion and permanently discontinue
KEYTRUDA.

Immune-mediated complications, including fatal events, occurred in
patients who underwent allogeneic hematopoietic stem cell
transplantation (HSCT) after treatment with KEYTRUDA. Of 23 patients
with cHL who proceeded to allogeneic HSCT after KEYTRUDA, 6 developed
graft-versus-host disease (GVHD) (one fatal case) and 2 developed severe
hepatic veno-occlusive disease (VOD) after reduced-intensity
conditioning (one fatal case). Cases of fatal hyperacute GVHD after
allogeneic HSCT have also been reported in patients with lymphoma who
received a PD-1 receptor–blocking antibody before transplantation.
Follow patients closely for early evidence of transplant-related
complications such as hyperacute GVHD, Grade 3 to 4 acute GVHD,
steroid-requiring febrile syndrome, hepatic VOD, and other
immune-mediated adverse reactions, and intervene promptly.

In clinical trials in patients with multiple myeloma, the addition of
KEYTRUDA to a thalidomide analogue plus dexamethasone resulted in
increased mortality. Treatment of these patients with a PD-1 or PD-L1
blocking antibody in this combination is not recommended outside of
controlled clinical trials.

Based on its mechanism of action, KEYTRUDA can cause fetal harm when
administered to a pregnant woman. If used during pregnancy, or if the
patient becomes pregnant during treatment, apprise the patient of the
potential hazard to a fetus. Advise females of reproductive potential to
use highly effective contraception during treatment and for 4 months
after the last dose of KEYTRUDA.

It is not known whether KEYTRUDA is excreted in human milk. Because many
drugs are excreted in human milk, instruct women to discontinue nursing
during treatment with KEYTRUDA and for 4 months after the final dose.

Merck’s Focus on Cancer

Our goal is to translate breakthrough science into innovative oncology
medicines to help people with cancer worldwide. At Merck, helping people
fight cancer is our passion and supporting accessibility to our cancer
medicines is our commitment. Our focus is on pursuing research in
immuno-oncology and we are accelerating every step in the journey – from
lab to clinic – to potentially bring new hope to people with cancer.

As part of our focus on cancer, Merck is committed to exploring the
potential of immuno-oncology with one of the fastest-growing development
programs in the industry. We are currently executing an expansive
research program evaluating our anti-PD-1 therapy across more than 30
tumor types. We also continue to strengthen our immuno-oncology
portfolio through strategic acquisitions and are prioritizing the
development of several promising immunotherapeutic candidates with the
potential to improve the treatment of advanced cancers.

At Merck, we are committed to supporting accessibility to our cancer
medicines. Merck provides multiple programs to help ensure that
appropriate patients who are prescribed KEYTRUDA have access to our
anti-PD-1 therapy. The Merck Access Program provides reimbursement
support for patients receiving KEYTRUDA, including information to help
with out-of-pocket costs and co-pay assistance for eligible patients.
Merck also offers free product through our patient assistance program to
eligible patients, primarily the uninsured, who, without our assistance,
could not afford their medicine. More information is available by
calling 855-257-3932 or visiting www.merckaccessprogram-keytruda.com.

About Merck’s Patient Support Program for KEYTRUDA

Merck is committed to helping provide patients and their caregivers
support throughout their treatment with KEYTRUDA. The KEY+YOU Patient
Support Program provides a range of resources and services. For further
information and to sign up, patients and physicians may call 85-KEYTRUDA
(855-398-7832) or visit www.keytruda.com.

About Merck

For more than a century, Merck, a leading global biopharmaceutical
company known as MSD outside of the United States and Canada, has been
inventing for life, bringing forward medicines and vaccines for many of
the world’s most challenging diseases. Through our prescription
medicines, vaccines, biologic therapies and animal health products, we
work with customers and operate in more than 140 countries to deliver
innovative health solutions. We also demonstrate our commitment to
increasing access to health care through far-reaching policies, programs
and partnerships. Today, Merck continues to be at the forefront of
research to advance the prevention and treatment of diseases that
threaten people and communities around the world - including cancer,
cardio-metabolic diseases, emerging animal diseases, Alzheimer’s disease
and infectious diseases including HIV and Ebola.

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